The relationship between birth weight and adult metabolic syndrome is a U-shaped curve. Both, low and high birth weights have been linked to adult obesity, suggesting increased risk at both ends of the spectrum. Thus, reductions from optimal growth in utero, be it from constrained growth (e.g., maternal preeclampsia, nicotine) or excessive growth (e.g., maternal obesity, diabetes) increases the relative risk of adult metabolic syndrome. Further, postnatal excess nutrition or rapid catch-up growth is an additive risk factor. To simulate this scenario, we have developed two rat models, one of maternal under-nutrition and one of overnutrition. Our previous model of maternal food restriction (FR) during pregnancy results in low birth weight newborns. When provided normal nursing and postweaning diet, these offspring exhibit rapid catch-up growth and adult obesity with lipid abnormalities. In contrast, our recent model of maternal obesity and high fat diet during pregnancy (HF) results in normal birth weight newborns. However, with continued nursing by HF dams, these offspring demonstrate accelerated growth and early onset of obesity with lipid abnormalities, evident by 3 weeks of age. Despite the putative nutrition differences, our studies indicate that the mechanism(s) of increased adiposity in FR and HF offspring is a result of programmed upregulation (at birth, prior to the development of obesity) of the adipogenesis signaling cascade. Specifically, at one day of life, both FR and HF offspring exhibit increased adipose tissue PPAR?2 gene expression with downregulation of co-repressor NCoR, and upregulation of co-activator SRC1. Thus, the changes in co-regulators may well be the fundamental underlying factor(s) contributing to programmed adiposity, though we postulate that this occurs via different mechanisms under nutrient limitation or nutrient excess. We hypothesize that (1) downregulation of NCoR and/or upregulation of SRC1 is the mechanism for PPAR?2 mediated adipogenesis in HF and FR offspring, and (2) epigenetic modification of these factors explains the altered gene expression, as well as offering the opportunity for preventative or therapeutic interventions. We will determine the underlying mechanism(s) for this paradoxical upregulation of PPAR?2 in programmed obesity. We will elucidate the role of PPAR?2 corepressors (NCoR, SIRT1, SMRT) and co-activators (SRC1, TIF2), and determine whether epigenetic modification of these factors and/or PPAR?2 is the mechanism for programmed adiposity. We will systematically address this by identifying the specific role of PPAR?2 co-repressors, co-activators and epigenetic modulation, and study the effects on its downstream lipid target. We will suppress PPAR?2 directly or via its co-repressor and determine the adipogenic and lipogenic effects. Lastly, we will test the inheritance of epigenetic modification in F2 progeny. We will contrast the mechanisms of programmed adipogenesis versus diet-induced metabolic syndrome (DIMS). These studies will provide new insights, and potential therapeutic interventions for gestationally programmed adipogenic mechanisms that lead to childhood and adult obesity.